The CF Foundation’s Newborn Screening Committee developed a consensus guideline with seven recommendations to describe current best practices in newborn screening nationwide.


RT’s Three Key Takeaways:

  1. The Cystic Fibrosis Foundation has released a seven-point consensus guideline to standardize and improve cystic fibrosis newborn screening across all US states.
  2. The recommendations aim to increase screening accuracy, equity, and timeliness by addressing issues like limited variant testing and inconsistent laboratory practices.
  3. The Foundation is supporting implementation through toolkits, funding, and collaborations to help states adopt best practices and reduce disparities in CF diagnoses.

The International Journal of Neonatal Screening, an international, peer-reviewed journal focused on newborn screening and medicine, published Cystic Fibrosis Newborn Screening: A Systemic Review-Driven Consensus Guideline from the United States Cystic Fibrosis Foundation. The guideline — a set of recommendations for practice that are created and agreed upon by a group of experts and specialists after reviewing published evidence — represents a significant milestone of the Foundation’s Newborn Screening Initiative, a multi-year effort to advance CF newborn screening and achieve better health outcomes for all babies born with the disease, regardless of background.  

Every state in the US performs newborn screening for cystic fibrosis. However, how that screen is done varies from state to state. The Foundation’s Newborn Screening Committee—comprising external experts, clinical partners, CF Foundation staff, and parents of children with CF—developed a consensus guideline with seven recommendations to describe current best practices in newborn screening nationwide. 

“Newborn screening can be a great equalizer for lifelong health outcomes, but the present system with its varied practices has only increased health disparities for CF newborns,” said Albert Faro, MD, senior vice president and chief medical officer of the Cystic Fibrosis Foundation. “Our efforts to improve this process are critical to advance our mission of providing all people with CF the opportunity to lead long, fulfilling lives.”   

CF Newborn Screening Process

Newborn screening occurs during the first few days of a baby’s life. A few drops of blood from a heel prick are placed on a special card and mailed to a state laboratory to test the blood sample for specific health conditions, including cystic fibrosis.  

The CF-specific test assesses the level of a chemical made by the pancreas called immunoreactive trypsinogen (IRT). In people with cystic fibrosis, IRT levels tend to be higher than average. Still, other factors — including circumstances around the baby’s birth — may play a role in higher levels of IRT. If an infant has elevated IRT levels, states then screen for CFTR variants before making a referral for a sweat test to make a CF diagnosis. If variants are identified, those results are shared with relevant health care professionals.  

Newborn Screening Consensus Guideline Recommendations

The guideline provides recommendations for states in the U.S. to improve CF newborn screening at each step of the current process as outlined above. All seven recommendations were approved unanimously by the Newborn Screening Initiative Committee. 

  • Recommendation 1 discusses examining a baby’s IRT level by taking an average of the values from other newborn blood spot samples collected that day. This allows the lab to assess if the baby’s IRT levels are too high.
  • Recommendation 2 discusses using a very high IRT level referral strategy when a state’s NBS program does not test for all CF-causing variants identified in the CFTR2 database or does not have a variant panel that identifies most people from the different ancestral groups within the state. This “very high IRT level” referral strategy refers to states’ labs setting an upper limit, so even if a baby does not have any CFTR variants found on the screen, they can still progress to the next step in the newborn screening process.
  • Recommendation 3 urges states not to use a NBS algorithm that only looks at the most common variant found in the CF population, F508del. The use of single-variant algorithms is rare.
  • Recommendation 4 discusses screening for the more than 1,100 CF-causing CFTR variants in the CFTR2 database.
  • Recommendation 5 discusses the need for states to conduct the CFTR variant screening step in their newborn screening algorithm at least twice a week as resources allow.
  • Recommendation 6 discusses including a genetic sequencing process following IRT and variant panel testing to improve the likelihood that a baby with CF and a rarer variant receives a positive screen.
  • Recommendation 7 discusses the importance of notifying both the primary care provider and the CF specialist if the newborn screen shows that the baby may have CF. 

Implementing these recommendations may improve sensitivity, equity, and timeliness of CF newborn screening, leading to improved health outcomes for all individuals diagnosed with the disease following a positive newborn screen and decreasing the burden on families.

What’s Next in CF Newborn Screening

Through the Foundation’s Screening Improvement Program Award for Optimizing the Diagnosis of Infants (SIP award), the Foundation funds clinicians, state labs, and researchers seeking to improve newborn screening systems across the US. Since 2011, the Foundation has funded more than $3.5 million across 48 awards and will fund a new set of projects in December.

While the guideline has been published, there is still more work ahead for the Newborn Screening Initiative. To support implementation of the recommendations, the Foundation developed a toolkit to help CF care teams engage with newborn screening programs and work together to advance newborn screening in their state. The Foundation is also funding newborn screening collaboratives for CF care teams and state programs to come together and discuss implementing the guideline recommendations, challenges they are facing, and improvements they are working on.

“We recognize that states are starting in different places and have varying abilities to implement these recommendations,” said Mary Dwight, senior vice president and chief policy and advocacy officer of the Cystic Fibrosis Foundation. “Our role, beyond publishing these recommendations, is to support CF care providers in partnering with state newborn screening programs to map out a plan for equitable and timely newborn screening now and in the future.”